RESUMEN
Patients with myasthenia gravis (MG) with antibodies to muscle-specific receptor tyrosine kinase (MuSK) differ from acetylcholine receptor (AChR)-positive MG patients, as they frequently present with severe oculobulbar muscle weakness or with neck, shoulder, and respiratory muscle involvement. The neuromuscular junction (NMJ) has been confirmed to be the main target of both AChR- and MuSK-MG. However, histopathological investigation disclosed that muscle fiber atrophy was prevalent in AChR-MG, whereas mild myopathic changes and mitochondrial abnormalities were more frequently observed in MuSK-MG. As the pathogenetic mechanism in MuSK-MG remains unclear, this study investigated the submicroscopic pattern of muscle histopathology to establish a possible correlation between clinical involvement and subcellular morphological findings. Muscle biopsies from seven MuSK-MG patients and from seven patients with AChR-MG were analyzed by transmission electron microscopy. Myopathic and mitochondrial abnormalities were more prominent in MuSK-MG and show giant, swollen, and degenerated mitochondria with fragmented cristae. The most common changes in AChR-MG muscles were fiber atrophy, myofibrillar disarray, and Z-line streaming, consistent with mild neurogenic abnormalities. A different pathogenetic mechanism is emerging in MuSK-MG compared to AChR-MG. Mitochondrial abnormalities seem to be more prominent in MuSK-MG, whereas neurogenic atrophy is observed in AChR-MG.
Asunto(s)
Autoanticuerpos/inmunología , Músculo Esquelético/ultraestructura , Miastenia Gravis/inmunología , Miastenia Gravis/patología , Adulto , Anciano , Autoantígenos/inmunología , Femenino , Humanos , Masculino , Microscopía Electrónica de Transmisión , Persona de Mediana Edad , Mitocondrias/ultraestructura , Unión Neuromuscular/inmunología , Unión Neuromuscular/patología , Proteínas Tirosina Quinasas Receptoras/inmunología , Receptores Colinérgicos/inmunología , Adulto JovenRESUMEN
Repeat instability is an important form of mutation that is responsible for several neurological, neurodegenerative and neuromuscular disorders. In this study we identified an unstable [CCTG](n) repeat in the second intron of the ZNF291 gene, on chromosome 15q21-24. The repeat number is polymorphic in normal population and the ZNF291 transcript is expressed in different areas of human brain, skeletal muscle and heart. These findings suggest that ZNF291 gene should be taken in consideration as an attractive candidate for neuromuscular expansion related diseases mapping in this locus.